Genetic Variant NM_001374.3:c.809A>C (chr16-2237984-A-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001374.3(DNASE1L2):c.809A>C(p.Asp270Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,454,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DNASE1L2
NM_001374.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.59

Publications

0 publications found

Variant links:

Genes affected

DNASE1L2 (HGNC:2958): (deoxyribonuclease 1 like 2) Predicted to enable DNA binding activity and deoxyribonuclease I activity. Predicted to be involved in DNA catabolic process, endonucleolytic. Predicted to act upstream of or within corneocyte development and hair follicle development. Predicted to be located in cytoplasm and extracellular region. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DNASE1L2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4020906).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNASE1L2	NM_001374.3	MANE Select	c.809A>C	p.Asp270Ala	missense	Exon 6 of 7	NP_001365.1	Q92874-1
	DNASE1L2	NM_001301680.2		c.809A>C	p.Asp270Ala	missense	Exon 6 of 7	NP_001288609.1	Q92874-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNASE1L2	ENST00000320700.10	TSL:1 MANE Select	c.809A>C	p.Asp270Ala	missense	Exon 6 of 7	ENSP00000316938.5	Q92874-1
DNASE1L2	ENST00000564065.5	TSL:1	c.809A>C	p.Asp270Ala	missense	Exon 5 of 6	ENSP00000454562.1	Q92874-1
DNASE1L2	ENST00000567494.5	TSL:1	c.809A>C	p.Asp270Ala	missense	Exon 6 of 7	ENSP00000455358.1	Q92874-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000867

AC:

AN:

230734

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000600

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1454072

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723068

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33278

American (AMR)

AF:

0.0000454

AC:

AN:

44066

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25986

East Asian (EAS)

AF:

0.00

AC:

AN:

39366

South Asian (SAS)

AF:

0.00

AC:

AN:

85312

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5094

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109634

Other (OTH)

AF:

0.00

AC:

AN:

60014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000834

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.79

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.75

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.53

MutationAssessor

Uncertain

2.3

PhyloP100

1.6

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.40

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.011

Polyphen

0.71

Vest4

0.55

MutPred

0.61

Gain of helix (P = 0.062)

MVP

0.71

MPC

0.72

ClinPred

0.86

GERP RS

4.5

Varity_R

0.28

gMVP

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over